BIOCHEMICAL ANTAGONISM 



lar demonstrations in lower forms. Perhaps we feel closer kinship 

 with the higher phyla, but more probably we sense the wider ranj^e of 

 observation possible in tests with mammals. Be that as it may, 

 Woolley and White reported that the feeding of minute amounts of 

 pyrithiamin to mice caused the appearance of typical signs of thiamin 

 deficiency in these animals. 



When mice are fed a thiamin-deficient diet, tliey do not exhibit most 

 of the characteristic signs which accompany thiamin deprivation in certain 

 other species. The fact that pyrithiamin evoked most of these signs may be 

 of use in the study of manifestations of deficiency in varied species. This idea 

 is strengthened by the observations that antagonistic analogues of some of the 

 other vitamins likewise produce typical signs of deficiency in species in which 

 such signs have not been seen previously. 



The disease was prevented or cured by sufficient amounts of 

 thiamin. Pyrithiamin is the analogue of thiamin in which the thiazole 

 ring is replaced by a pyridine ring, or, more specifically, the sulfur atom 

 is replaced by — CH=CH — . It was then shown that glucoascorbic 

 acid, a structural analogue of ascorbic acid, produced a scurvylikc 

 disease of rats, mice, and guinea {ligs, and that, in guinea pigs, tlie 

 disea.se was prevented by adequate amounts of ascorbic acid. Fur- 

 thermore, signs of riboflavin deficiency were produced m rats by feeding 

 isoriboflavin, and in mice by feeding 2,4-dinitro-7,8-dimethyl-10- 

 ribityl-5,10-dihydrophenazine, the phcnazine analogue of riboflavin. 

 Moreover, manifestations of nicotinic acid deficiency were brought 

 about in mice by feeding 3-acetylpyridine, and prevented with nico- 

 tinic acid. Shortly before this, it was realized that the signs pre- 

 cipitated by 3,3'-methylenebis-[4-hydroxycoumarin] were those of 

 vitamin K deficiency and were preventable by the vitamin to which 

 the coumarin bears structural analogy. Finally, several results of 

 tocopherol and vitamin K deficiencies were produced in mice by 

 feeding tocopherol quinone. 



Interspersed with these observations on animals there have been 

 a long series of findings of similar nature on the reversible inhibition 

 of microbial growth. It is not the purpose of this essay to catalogue 

 the rather impressive number of individual findings in this regard, but 

 rather to attempt to discover what general principles may lie beneath 

 them. Therefore, it will suffice to recount that 3-pyridincsuIfonic acid 



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